Expandable catheter system for vessel wall injection and muscle and nerve fiber ablation

ABSTRACT

A catheter-based/intravascular ablation (denervation) system includes a multiplicity of needles which expand open around a central axis to engage the wall of a blood vessel, or the wall of the left atrium, allowing the injection of a cytotoxic or/or neurotoxic solution for ablating conducting tissue, or nerve fibers around the ostium of the pulmonary vein, or circumferentially in or just beyond the outer layer of the renal artery. The expandable needle delivery system is formed with self-expanding materials and include structures, near the end portion of the needles, or using separate guide tubes. The system also includes means to limit and/or adjust the depth of penetration of the ablative fluid into the tissue of the wall of the targeted blood vessel.

REFERENCE TO RELATED APPLICATIONS

This Application is being filed as a Continuation-in-Part of patentapplication Ser. No. 13/216,495, filed 24 Aug. 2011, currently pending.

FIELD OF USE

This invention is in the field of devices to ablate muscle cells andnerve fibers for the treatment of cardiac arrhythmias, hypertension,congestive heart failure and other disorders.

BACKGROUND OF THE INVENTION

Since the 1930s it has been known that injury or ablation of thesympathetic nerves in or near the outer layers of the renal arteries candramatically reduce high blood pressure. At the present time, physiciansoften treat patients with atrial fibrillation (AF) using radiofrequency(RF) catheter systems to ablate conducting tissue in the wall of theleft atrium of the heart around the ostium of the pulmonary veins.Similar technology, using radiofrequency energy, has been successfullyused inside the renal arteries to ablate sympathetic and other nervefibers that run in the outer wall of the renal arteries, in order totreat high blood pressure. In both cases these are elaborate andexpensive catheter systems that can cause thermal, cryoablative, orother methods to injure surrounding tissue. Many of these systems alsorequire significant capital outlays for the reusable equipment that liesoutside of the body, including RF generation systems and the fluidhandling systems for cryoablative catheters.

Because of the similarities of anatomy, for the purposes of thisdisclosure, the term target wall will refer here to either the wall ofthe left atrium surrounding a pulmonary vein or the wall of a pulmonaryvein near its ostium for AF ablation applications or the wall of theaorta around the ostium of the renal artery, or within the renal arteryitself, for hypertension or congestive heart failure (CHF) applications.

In the case of atrial fibrillation ablation, the ablation of tissuesurrounding multiple pulmonary veins can be technically challenging andvery time consuming. This is particularly so if one uses RF cathetersthat can only ablate one focus at a time. There is also a failure rateusing these types of catheters for atrial fibrillation ablation. Thefailures of the current approaches are related to the challenges increating reproducible circumferential ablation of tissue around theostium (peri-ostial) of a pulmonary vein. There are also significantsafety issues with current technologies related to very long fluoroscopyand procedure times that lead to high levels of radiation exposure toboth the patient and the operator, and may increase stroke risk inatrial fibrillation ablation.

There are also potential risks using the current technologies for RFablation to create sympathetic nerve denervation from inside the renalartery for the treatment of hypertension or congestive heart failure.The short-term complications and the long-term sequelae of applying RFenergy from inside the renal artery to the wall of the artery are notwell defined. This type of energy applied within the renal artery, andwith transmural renal artery injury, may lead to late restenosis,thrombosis, renal artery spasm, embolization of debris into the renalparenchyma, or other problems inside the renal artery. There may also beuneven or incomplete sympathetic nerve ablation, particularly if thereare anatomic anomalies, or atherosclerotic or fibrotic disease insidethe renal artery, such that there is non-homogeneous delivery of RFenergy This could lead to treatment failures, or the need for additionaland dangerous levels of RF energy to ablate the nerves that run alongthe adventitial plane of the renal artery.

The currently used system for RF energy delivery also does not allow forefficient circumferential ablation of the renal sympathetic nervefibers. If circumferential RF energy were applied in a ring segment fromwithin the renal artery (energy applied at intimal surface to killnerves in the outer adventitial layer) this could lead to even higherrisks of renal artery stenosis from the circumferential and transmuralthermal injury to the intima, media and adventitia. Finally, the“burning” or the inside of the renal artery using RF ablation can beextremely painful. Thus, there are numerous and substantial limitationsof the current approach using RF-based renal sympathetic denervation.

The Bullfrog® micro infusion catheter described by Seward et al in U.S.Pat. Nos. 6,547,803 and 7,666,163 which uses an inflatable elasticballoon to expand a single needle against the wall of a blood vesselcould be used for the injection of an chemical ablative solution such asalcohol but it would require multiple applications as it does notdescribe or anticipate the circumferential delivery of an ablativesubstance around the entire circumference of the vessel. The most numberof needles shown by Seward is two and the two needle version of theBullfrog® would be hard to miniaturize to fit through a small guidingcatheter to be used in a renal artery. If only one needle is used,controlled and accurate rotation of any device at the end of a catheteris difficult at best and could be risky if the subsequent injections arenot evenly spaced. This device also does not allow for a precise,controlled, and adjustable depth of delivery of a neuroablative agent.Another limitation of the Bullfrog® is that inflation of a balloonwithin the renal artery can induce stenosis due to balloon injury of theintima and media of the artery, as well as causing endothelial celldenudation.

Jacobson and Davis in U.S. Pat. No. 6,302,870 describe a catheter formedication injection into the inside wall of a blood vessel. WhileJacobson includes the concept of multiple needles expanding outward,each with a hilt to limit penetration of the needle into the wall of thevessel, his design depends on rotation of the tube having the needle atits distal end to allow it to get into an outward curving shape. Thehilt design shown of a small disk attached a short distance proximal tothe needle distal end has a fixed diameter which will increase the totaldiameter of the device by at least twice the diameter of the hilt sothat if the hilt is large enough in diameter to stop penetration of theneedle, it will significantly add to the diameter of the device. Foreither the renal denervation or atrial fibrillation application, thelength of the needed catheter would make control of such rotationdifficult. In addition, the hilts which limit penetration are a fixeddistance from the distal end of the needles. There is no built inadjustment on penetration depth which may be important if one wishes toselectively target a specific layer in the blood vessel or if one needsto penetrate all the way through to the volume past the adventitia invessels with different wall thicknesses. Jacobson also does not envisionuse of the injection catheter for denervation. Finally, Jacobson in FIG.3 when he shows a sheath over expandable needles, there is no guide wireand the sheath has an open distal end which makes advancement throughthe vascular system more difficult. Also the needles if they werewithdrawn completely inside of the sheath they could because of thehilts, get stuck inside the sheath and be difficult to push out.

The prior art also does not envision use of anesthetic agents such aslydocaine which if injected first or in or together with an ablativesolution can reduce or eliminate any pain associated with thedenervation procedure.

Finally, while injection of ethanol as an ablative substance is wellknown and used within the heart and other parts of the body, there hasbeen no development of an ethanol (or other liquid nerve ablationsubstances) injection system specifically designed for thecircumferential ablation of sympathetic nerve fibers around the renalarteries.

SUMMARY OF THE INVENTION

The present invention, Intravascular Nerve Ablation System (INAS), iscapable of applying an ablative fluid to produce circumferential damagein the nerve tissue that is in or near the wall of a blood vessel with arelatively short treatment time using a disposable catheter andrequiring no additional capital equipment. The primary focus of use ofINAS is in the treatment of cardiac arrhythmias, hypertension andcongestive heart failure. Unlike the Bullfrog or RF ablation devicesthat work with one or, at most two points of ablation, the presentinvention is designed to provide a more uniform circumferential injuryto the nerves, while minimizing injury to the intima and medial layersof the vessel wall. The term circumferential delivery is defined here asat least three points of simultaneous injection of a suitable ablativesolution within a vessel wall, or circumferential filling of the spaceoutside of the adventitial layer (outer wall) of a blood vessel. Unlikethe Jacobson device of U.S. Pat. No. 6,302,870, which does describecircumferential delivery, the present invention does not depend uponrotation of a tube to create outward movement nor does it have a fixeddiameter hilt to limit penetration.

Specifically, there is a definite need for such a catheter system thatis capable of highly efficient, and reproducible ablation of the nervessurrounding the renal artery ostium, or distal to the ostium in therenal artery wall, in order to damage the sympathetic nerve fibers thattrack from the peri-ostial aortic wall into the renal arteries, and thusimprove the control and treatment of hypertension, etc.

This type of system may also have major advantages over other currenttechnologies by allowing highly efficient, and reproduciblecircumferential ablation of the muscle fibers and conductive tissue inthe left atrium, surrounding the ostium of the pulmonary veins or in thewall of the pulmonary veins near or at their ostium into the left atriumof the heart. Such ablation could interrupt atrial fibrillation (AF) andother cardiac arrhythmias. Other potential applications of this approachmay evolve.

The present invention is a small (<2 mm diameter) catheter, whichincludes multiple expandable injector tubes, or guide tubes to allowpassage of coaxial injector tubes, arranged circumferentially around thebody of the INAS near its distal end. Each injector tube includes aneedle at its distal end. Ablative fluid could be injected through thedistal end of this needle which has injection egress through its distalend or through side holes placed just proximal to its distal end, needlehas a (solid tipped) cutting distal end. There is a penetration limitingmember as part of the INAS so that the needles will only penetrate intothe tissue of the wall of the target blood vessel to a preset distance.These may be a preset distance proximal to the distal end of each needlesimilar to the hilts of the Jacobson et al patent or the penetrationlimiting member may be built into the proximal section of the INAS.Limiting penetration is important to reduce the likelihood ofperforation of the vessel wall, optimize the depth of injection or toadjust the depth to be into the volume just outside of the blood vesselwall. In a preferred embodiment for renal sympathetic nerve ablation,self-expanding guiding tubes are first deployed against the inside wallof the renal artery and act as a guide for separate coaxiallylongitudinally moveable injector tubes with sharpened needles withinjection egress port(s) near the distal end.

The penetration limiting function of the present invention INAS asdescribed herein uses one of the following techniques that will greatlyreduce the diameter of the device as compared with the Jacobson designsof U.S. Pat. No. 6,302,870 and thus also improve the ability to deliverit into a vessel of a human body such as the renal artery. Thesetechniques include:

-   -   Use of a cord or wire attached to the multiple needles that can        fold during insertion to limit the diameter of the distal        section of the INAS,    -   Use of one, two or more short NITINOL wires attached in the        longitudinal direction at their proximal ends to the sides of        the needle. The wires being designed to have their distal ends        not be attached and having a memory state that curves away from        the needle so as to act as a penetration limiting member for the        needle. Such wires would fold tight against the needles to        reduce the diameter of the distal section of the INAS,    -   Use of two bends in the needle the bend forming the penetration        limiting member and the bend also being in the circumferential        direction so as to not increase the diameter of the distal        section of the INAS, and    -   Use of guide tubes that curve outward through which the needles        slide in the longitudinal direction. The limit for penetration        in this design is integral into the handles at the proximal end        of the INAS and do not require diametric volume in the distal        section of the INAS. This last embodiment has the added        advantage of allowing adjustment of the penetration depth.

The injector tubes with distal needles are in fluid communication withan injection lumen in the catheter body, which is in fluid communicationwith an injection port at the proximal end of the INAS. Such aninjection port would typically include a standard connector such as aLuer connector used to connect to a source of ablative fluid.

This injection system also anticipates the use of very small gaugeneedles (smaller than 25 gauge) to penetrate the arterial wall, suchthat the needle penetration could be safe, even if targeted to a planeor volume of tissue that is at, or deep to (beyond) the adventitiallayer of the aorta, a pulmonary vein or renal artery. It is alsoanticipated that the distal needle could be a cutting needle rather thana coring needle and that the injection egress ports could be smallinjection holes (pores) cut into the sides of the injector tubes ordistal needle, proximal to the cutting needle tip.

The expandable injector tubes or guide tubes may be self-expanding madeof a springy material, a memory metal such as NITINOL or they may bemade of a metal or plastic and expandable by other mechanical means. Forexample, the expandable legs with distal injection needles could bemounted to the outside of an expandable balloon whose diameter iscontrollable by the pressure used to inflate the balloon. There shouldbe at least 2 injector tubes but 3 to 8 tubes may be more appropriate,depending on the diameter of the vessel to be treated. For example, in a5 mm diameter renal artery, only 3 or 4 needles may be needed while inan 8 mm diameter renal one might need 6 needles.

The entire INAS is designed to include a fixed distal guide wire or beadvanced over a guide wire in either an over-the-wire configurationwhere the guide wire lumen runs the entire length of the INAS or a rapidexchange configuration where the guide wire exits the catheter body atleast 10 cm distal to the proximal end of the INAS and runs outside ofthe catheter shaft for its proximal section. The fixed wire version ispreferred as it would have the smallest distal diameter.

The INAS would also include a tubular, thin-walled sheath thatconstrains the self-expanding injection tubes with distal needles and/orguiding tubes prior to deployment, and for removal from the body. Thesheath also allows the distal end of the INAS to be inserted into theproximal end of a guiding catheter or introducer sheath. The sheath alsoserves to protect the operator(s) from possible needle sticks andexposure to blood borne pathogens at the end of the procedure when theINAS is removed from the patient's body.

It is also envisioned that the injection needles, guiding tubes andinjection tubes could be formed from a radiopaque material such astantalum or tungsten or coated, or marked with a radiopaque materialsuch as gold or platinum so as to make them clearly visible usingfluoroscopy.

It is also envisioned that one or more of the injector needles could beelectrically connected to the proximal end of the INAS so as to also actas a diagnostic electrode(s) for evaluation of the electrical activityin the area of the vessel wall.

It is also envisioned that one could attach 2 or more of the expandablelegs to an electrical or RF source to deliver electric current or RFenergy around the circumference of a target vessel to the ostial wall toperform tissue and/or nerve ablation.

It is also envisioned that this device could utilize one, or more thanone neuroablative substances to be injected simultaneously, or in asequence of injections, in order to optimize permanent sympathetic nervedisruption in a segment of the renal artery (neurotmesis). Theanticipated neurotoxic agents that could be utilized includes but is notlimited to ethanol, phenol, glycerol, local anesthetics in relativelyhigh concentration (e.g., lidocaine, or other agents such asbupivicaine, tetracaine, benzocaine, etc.), anti-arrhythmic drugs thathave neurotoxicity, botulinum toxin, guanethidine, heated fluidsincluding heated saline, hypertonic saline, KCI or heated neuroablativesubstances such as those listed above.

The present invention also envisions use of anesthetic agents such aslydocaine which if injected first or in or together with an ablativesolution can reduce or eliminate any pain associated with thedenervation procedure.

It is also envisioned that one could utilize imaging techniques such asmultislice CT scan, MRI or intravascular ultrasound imaging to get anexact measurement of the thickness and anatomy of the target vessel wall(e.g., renal artery) such that one could know and set the exact andcorrect penetration depth for the injection of the ablative agent priorto the advancement of the injector needles or injector tubes. The use ofIVUS prior to use of the INAS may be particularly useful in order totarget the exact depth intended for injection. This exact depth can thenbe targeted using the adjustable depth of penetration feature in ourpreferred embodiment(s). The selection of penetration depth can beaccomplished using the proximal handles of the guide tube embodiment orby selection of an appropriate product code for the other designs thatmight have two to five versions each with a different penetration depthlimit.

For use in the treatment of hypertension or CHF, via renal sympatheticnerve ablation, the present preferred embodiment of this invention INASwould be used with the following steps:

-   -   1. Engage a first renal artery with a guiding catheter placed        through the femoral artery.    -   2. Advance the distal end of the INAS with a fixed distal        guidewire into, and advance the INAS through the guiding        catheter, until the distal end of the guiding tubes are passed        beyond the distal end of the guiding catheter and into the renal        artery.    -   3. Pull back the sheath allowing the expandable guide tubes to        open up until the distal ends of the guide tubes press outward        against the inside wall of the renal artery.    -   4. With the injector guide tubes having an outward curve or        angle, the guide tube handle that controls the longitudinal        motion of the guide tubes is then moved in the distal direction        allowing the distal ends of the guide tubes that are touching        the inside wall of the renal artery to further press against the        intima and begin to flex backwards.    -   5. The guide tubes will then have their open distal ends facing        into the renal artery wall. At this point contrast injection        from the guiding catheter can confirm the correct spacing and        position of the guide tubes.    -   6. Next, the injection tubes are be advanced coaxially through        the guide tubes to an adjustable distance with a target of        placing the injection egress to be at or just deep to the        adventitial plane of the renal; artery. One or more penetrating        limiting member(s) will allow the needles only to penetrate a        preset distance (typically between 0.5 to 3 mm but preferably        about 2-3 mm) into the vessel wall of the renal artery. Ideally,        the very small gauge injection needles may be advanced to ˜2-3        mm depth in the renal artery to deliver the neuroablative        agent(s) at or deep to the adventitial plane, in order to        minimize intimal and medial renal artery injury. The correct        depth can be determined prior to the INAS treatment using CT        scan, MRI or intravascular ultrasound to measure the renal        artery wall thickness, such that the correct initial depth        setting for the injector tube penetration is known prior to        advancing the needles.    -   7. Attach an injection system, syringe or multiple syringes        through a manifold to the connector at the INAS proximal end        used to supply the ablative fluid. An anesthetic agent such as        lidocaine can then be injected to eliminate or reduce any pain        associated with the denervation procedure. The anesthetic agent        can be injected before, after or at the same time as a small        volume of contrast would be injected through the system, exiting        at the injection egress near the distal end of the injector        tubes to confirm the correct depth for injection of the        neuroablative agent. Adjustment of the depth is possible at this        time if the injection plane is determined to be to shallow        (e.g., in media) or too deep (well outside the adventitial        plane).    -   8. Inject an appropriate volume of ethanol (ethyl alcohol),        phenol, glycerol, lidocaine, bupivacaine, tetracaine,        benzocaine, guanethidine, botulinum toxin or other appropriate        neurotoxic fluid, including a combination of 2 or more        neuroablative fluids or local anesthetic agents together or in        sequence (local anesthetic first to diminish discomfort,        followed by delivery of the ablative agent) and/or high        temperature fluids (or steam), or extremely cold (cryoablative)        fluid from the syringe or injection system through the catheter        and out of the needles into the vessel wall and/or the volume        just outside of the vessel. A typical injection would be        1-10 ml. This should produce a multiplicity of ablation zones        (one for each injector tube) that will intersect to form an        ablative ring around the circumference of the target vessel.        Contrast could be added to the injection either during a test        injection or during the therapeutic injection to allow x-ray        visualization of the ablation zone.    -   9. Once the injection is complete, retract the INAS injector        tubes back inside the guide tubes. Then, retract and re-sheath        the guide tubes by advancing the sheath over the guide tubes.        This will collapse the guide tubes back under the sheath. The        entire INAS can then be pulled back into the guiding catheter.    -   10. In some cases, one may rotate the INAS 20-90 degrees and        then repeat the injection if needed to make an even more        definitive ring of ablation.    -   11. The same methods as per prior steps can be repeated to        ablate tissue in the contralateral renal artery.    -   12. Remove the INAS from the guiding catheter completely.    -   13. Remove all remaining apparatus from the body.    -   14. A similar approach can be used with the INAS, via transeptal        access into the left atrium to treat AF, via ablation of tissue        in the vessel wall of one or more pulmonary veins. When        indicated, advance appropriate diagnostic electrophysiology        catheters to confirm that the ablation (in the case of atrial        fibrillation) has been successful

It is also envisioned that one could mount injector tubes with needleson the outer surface of an expandable balloon on the INAS in order todeliver 2 or more needles into the vessel wall of a target vessel toinject ablative fluid.

Although the main embodiment of this invention utilizes two or moreneedle injection sites to circumferentially administer alcohol or otherneuro-toxic fluid(s) to the wall of the renal artery for sympatheticnerve ablation, it is also envisioned that other modifications of thisconcept could also be utilized to achieve the same result. In one caseit is envisioned that circumferential fluid based (ethanol or otherablative fluid, a combination of ablative fluids, or heated fluid) couldbe administered in a circumferential fashion to a “ring segment” of therenal artery by injecting the ablative fluid into a space between twoinflated balloons. Thus, after inflating a proximal occlusive balloonand a distal occlusive balloon, the ablative fluid would be injectedinto the space between the two balloons and allowed to dwell for a shortperiod of time allowing the fluid, such as ethanol to penetrate throughthe arterial wall and reach the adventitial layer, thus disrupting andablating the sympathetic nerves running in this space. After the dwellperiod the space could be flushed with saline and the balloons deflated.

Similarly, a single balloon with a smaller diameter near the middle ofthe balloon could function in the same way, as the ethanol or otherablative fluid, or a combination of ablative fluids, or heated fluid isinjected in the “saddle-like” space in the central part of the balloonthat is not touching the arterial wall.

It is also envisioned that another embodiment may include acircumferential band of polymer, hydrogel or other carrier, on thecentral portion of an inflatable balloon with the carrier containing theneurotoxic agent(s), such as alcohol, phenol, glycerol, lidocaine,bupivacaine, tetracaine, benzocaine, guanethidine, botulinum toxin, etc.The balloon would be inflated at relatively low pressure to oppose theintimal surface of the renal arterial wall, and inflated for a dwelltime to allow penetration of the neurotoxic agent, circumferentially,into a “ring segment” of the renal artery and allow ablation of thesympathetic nerve fibers running near or in the adventitial plane.

It is also envisioned that the INAS catheter could be connected to aheated fluid, or steam, source to deliver high temperature fluids toablate or injure the target tissue or nerves. The heated fluid could benormal saline, hypertonic saline, alcohol, phenol, lidocaine, or someother combination of fluids. Steam injection, of saline, hypertonicsaline, ethanol, or distilled water or other fluids via the needlescould also be performed in order to achieve thermal ablation of targettissue or nerves at and around the needle injection sites.

It is also envisioned that the INAS could utilize very small diameterneedle injection tubes (e.g., 25-35 gauge) with sharpened needles attheir distal ends such that the needles would be advanced to, or eventhrough the adventitial plane of the renal artery or aortic wall using apenetration limiting member(s) or the combination of the guide tubeswith an adjustable depth advancement of injector tubes through the guidetubes in order to set the depth of penetration, and allow one to “bathe”the adventitial layer containing the sympathetic nerves with neurotoxicfluid, while causing minimal injury to the intimal and medial vesselwall layers, These very tiny needles could pass transmurally through thearterial wall yet create such tiny holes in the arterial wall that bloodleakage from the lumen to outside the vessel as well as medial layerinjury would be minimal, and thus safe. Thus, the present inventioncould have the injection be either into the wall of the renal artery,into the adventitia of the renal artery or deep to the adventitial layerof the renal artery such that the injection needles or egress frominjection tubes would occur via penetration all the way through thearterial wall to allow the ablative fluid to flow around and “bathe” theoutside of the artery with one or more neuroablative substances.

Another embodiment may include two or more pores, or small metallic(very short) needle like projections on the outer surface of the centralportion of an inflatable balloon, that would be in fluid communicationwith an injection lumen to allow injection into the wall of the renalartery and allow circumferential delivery of a neurotoxic agent(s).Given these teachings and embodiment descriptions, other similartechniques could be envisioned to allow other variations upon thisconcept of a balloon expandable, circumferential ablation system forrenal artery sympathetic nerve ablation.

Another embodiment of the present invention, as described in the methodsabove, places the means to limit penetration of the vessel wall at theproximal end of the INAS. In this embodiment, at least three guide tubeswith expandable distal portions run along the distal portion of thelength of the INAS. A guide tube handle with optional flushing port isattached to the proximal end of the INAS and controls the longitudinalmotion of the guide tubes.

One injection tube is included for each guide tube where the injectiontubes have sharpened (cutting needle) distal ends with injection egressports just proximal to the cutting needle tip. The injection tubes arelocated coaxially inside of the guide tubes. The distal ends of thesharpened injection needles at the distal ends of the injection tubesare initially “parked” just proximal to the distal end of the guidetubes. A proximal injection tube handle attached to the proximal end ofthe injection tubes, or to the proximal end of a single injector tubethat connects to the multiple injector tubes, is separated at its distalend from the proximal end of the guide tube handle forming a needleadvancement gap. The injector tube handle has means to adjust the needleadvancement gap distance. Alternately, the adjustment could be on theguide tube handle or a separate mechanism between the injector tubehandle and guide tube handle. A fitting for injection of an ablativefluid is attached to the injector tube handle and is in fluidcommunication with the injection lumens of the injector tubes.

In its initial configuration a sheath lies outside of the guide tubesconstraining them. The proximal end of the sheath is attached to asheath handle which can be locked down to prevent longitudinal motionwith respect to the guide tubes or unlocked to allow the sheath to bemoved in the proximal or distal direction to open and close the INAS.

The process to use the INAS handles is to have each of the lumens in theINAS flushed with normal saline. The distal end of the INAS is thenadvanced through a guiding catheter into a vessel such as a renalartery. The sheath control handle is then pulled back holding the guidetube handle in position. This will allow the distal portion of the guidetubes to expand outwardly against the wall of a vessel such as a renalartery. Optionally, after the sheath is pulled back, the guide tubes canthen be pushed slightly forward using the guide tube handle to ensurethey are engaged firmly against the vessel wall. The injector tubehandle is then advanced so as to push the distal ends of the injectiontubes having sharpened injection needles out of the distal end of theguide tubes which are touching the inside of the vessel wall. Theneedles will penetrate into the media of the vessel wall. Depending onthe advancement gap, the penetration of the needles into the vessel wallcan be limited. This can permit selective injection through theinjection egress ports of the needles into the media, adventitia,outside of the adventitia or any combination of these depending on thenumber and location of injection egress ports. After the needles areproperly placed into or through the vessel wall, a source of ablativefluid such as ethanol is attached to the fitting in the injection tubehandle and the fluid is injected through the lumens inside the injectortubes and out through the injection egress ports into the tissue.

After the injection is complete, the injection tube handle is pulledback to retract the needles into the distal portion of the guide tubes.The sheath control handle is then advanced to collapse the guide tubesand close the INAS. The sheath control handle is then locked down toprevent inadvertent opening of the INAS. The INAS is then pulled backonto the guiding catheter and the same procedure can be repeated for theother renal artery.

Although it is envisioned that there could be a number from one to 8injector tubes inside of 8 guide tubes, it is likely that 3 or 4 tubesis optimal for circumferential tissue ablation.

Thus it is an object of the present invention INAS is to have apercutaneously delivered catheter that can be used to treat atrialfibrillation with one, or more injections of an ablative fluid into thevessel walls of the pulmonary veins near the ostium, or into the leftatrial tissue surrounding one or more of the pulmonary veins.

Another object of the present invention INAS is to have a percutaneouslydelivered catheter that can be used to treat hypertension with one, ormore injections of an ablative fluid into or deep to, the vessel wall ofthe renal arteries, or into the wall of the aorta surrounding the ostiumof the renal artery.

Another object of the present invention INAS is to facilitate injectionof an ablative fluid into or beyond the outer layers of the renal arteryto reduce or prevent injury to the inner layers including the media ofthe renal artery.

Still another object of the present invention INAS is to have apercutaneously delivered catheter that includes a multiplicity ofcircumferentially expandable injector tubes, each tube having a needleat its distal end with injection egress allowing the delivery of anablative fluid into the wall of a target vessel or into the space beyondthe vessel wall.

Still another object of the invention is to have a flexible penetrationlimiting member or means attached just proximal to the distal end ofeach injector needle, or relatively blunt tipped guiding tubes to limitthe depth of needle penetration into, or just through, the vessel wall.

Still another object of the present invention is to have a sheath thatin conjunction with a distal tip provide for open and closed positionsof the INAS. The closed position has the sheath and distal tip touchingso as to totally enclose the sharpened needles while the open positionallows the needles to expand outward for injection of the ablative fluidinto or deep to the vessel wall.

Yet another object of the present invention is to use heated or cooledablative fluid to be the source of the tissue ablation such as withheated or cooled normal saline or enhance the efficacy of an alreadyablative fluid such as ethanol.

Yet another object of the present invention INAS is to have one or moreof the injector needles act as diagnostic electrodes for measurement ofelectrical activity within the wall of the target vessel.

Yet another object of this invention is to use a multiplicity ofcoaxially guided injector tubes that move slidably within correspondingexpandable guiding tubes, to allow the safe, controlled and adjustabledepth of passage of injector tubes with sharpened needles at theirdistal ends into and/or through the wall of a target vessel, to allowcontrolled chemoablation of nerves in the adventitial layer of an arterywhile minimizing intimal and medial injury of said artery.

Yet another object of the present invention is to provide injection ofan anesthetic agent before or during injection of the ablative fluid soas to prevent or reduce any pain associated with the denervationprocedure.

These and other objects and advantages of this invention will becomeobvious to a person of ordinary skill in this art upon reading of thedetailed description of this invention including the associateddrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a longitudinal cross section drawing of the distal portion ofthe present invention Vascular Nerve Ablation System (INAS) having afixed guide wire at its distal end.

FIG. 2 is a schematic view of the distal portion of the INAS in itsclosed position as it would be configured for delivery into the humanbody or to cover the injector needles during removal from the humanbody.

FIG. 3 is a schematic view of the distal portion of the INAS in its openposition as it would be configured for delivery of an ablative solutioninto the target vessel wall.

FIG. 4 is a longitudinal cross sectional drawing of the proximal end ofthe fixed wire embodiment of the INAS of FIGS. 1 through 3.

FIG. 5A is a schematic view of the distal portion of the closed INAS ofFIG. 2 as it is first advanced out of a guiding catheter into a renalartery.

FIG. 5B is a schematic view of the distal portion of the closed INAS asthe sheath is being pulled back to allow the expandable tubes openagainst the wall of the renal artery distal to the ostium.

FIG. 5C is a schematic view of the distal portion of the fully open INASof FIG. 3 with needles fully embedded into the wall of the renal arteryto allow the infusion of an ablative substance into the vessel wall.

FIG. 5D is a schematic view of the distal portion of the closed INAS asthe distal portion of the INAS is being pulled back into the sheath toclose the INAS either for subsequent use in the other renal artery orfor removal from the body.

FIG. 5E is a schematic view of the distal portion of the closed INAS ofFIG. 2 after it has been closed by retraction of the distal portion ofthe INAS into the sheath either for subsequent use in the other renalartery or for removal from the body.

FIG. 6 is a longitudinal cross section drawing of the embodiment of theINAS that is delivered over a separate guide wire.

FIG. 7 is a longitudinal cross sectional drawing of the proximal end ofan over-the-wire embodiment of the INAS of FIG. 6.

FIG. 8 is a longitudinal cross section drawing of an injector capable ofdelivering a heated ablative solution into the INAS of FIGS. 1-4.

FIG. 9 is a longitudinal cross section drawing of the proximal sectionof an injection needle showing longitudinal welded wire penetrationlimiting members.

FIG. 10 is a longitudinal cross section drawing of the proximal sectionof another embodiment of the present invention that delivers an ablativefluid circumferentially to the inside of a target vessel.

FIG. 11 is a longitudinal cross section of another embodiment of thepresent invention INAS in its closed position having four injector tubesthat can slide within four guide tubes. The injector tubes havesharpened needles having injection egress ports at the distal end ofeach injector tubes.

FIG. 12 is an enlargement of the area S12 of FIG. 11 showing the distalportion of the injector tubes and guide tubes.

FIG. 13 is a circumferential cross section at S13-S13 of the INAS ofFIG. 11

FIG. 14 is a longitudinal cross section of the expanded distal portionof the INAS.

FIG. 15 is an enlargement of the area S15 of FIG. 14.

FIG. 16 is a longitudinal cross section of the proximal end of the INASof FIGS. 11-15.

FIG. 17 is an enlargement of the area S17 of FIG. 16.

FIG. 18 is an enlargement of the area S18 of FIG. 16.

FIG. 19 is a longitudinal cross section of an alternate embodiment ofall but the distal portion of the INAS using multiple guide tubes.

FIG. 20. is a longitudinal cross section of a central transition portionconnecting the proximal portion of the of the INAS of FIG. 19 with thedistal portion of the INAS of FIGS. 11-14.

FIG. 21 is a circumferential cross section at S21-S21 of the INAScentral transition portion of FIG. 20.

FIG. 22 is a circumferential cross section at S22-S22 of the INAScentral transition portion of FIG. 20.

FIG. 23 is a circumferential cross section at S23-S23 of the INAScentral transition portion of FIG. 20.

DETAILED DESCRIPTION OF THE DRAWINGS

FIG. 1 is a longitudinal cross section drawing of the distal portion ofthe present invention Vascular Nerve Ablation System (INAS) 10 having afixed guide wire 25 with tip 28 at its distal end. FIG. 1 shows the INAS10 in its fully open position with the self-expanding injector tubes 15with distal ends sharpened to form injection needles 19 open to theirmaximum diameter. Flexible cords 13 with adhesive 14 that attaches thecords 13 to the injector tubes 15 act as a penetration limiting memberto prevent the distal tip of the needles 19 from penetrating more than amaximum distance L into a vessel wall. The injector tubes can be madefrom any springy material with the preferred material being NITINOL. Aseparate spring or inflatable balloon could be placed inside of theinjector tubes if the tubes are self-expanding to achieve the sameobjective. A balloon while increasing the diameter of the system wouldbe able to push the needles with great force into the vessel wall.

A sheath 12 with radiopaque marker 27 is shown in FIG. 1 in its positionwhere it has been pulled back to allow full expansion of the injectortubes 15. There are 4 injector tubes 15 in this embodiment of the INAS10 although as few as 2 and as many as 12 are envisioned. The distance Lcan be between 0.2 and 2 mm with the optimal being about 1 mm.

The distal section 20 of the INAS 10 includes the distal wire 25,tapered flexible tip 26, radiopaque maker 24 and sheath engagementsection 22 that assures that the distal portion of the INAS 10 willproperly pull back into the sheath 12 following use of the INAS 10 toablate tissue in a vessel of the human body. The INAS 10 is fully closedwhen the two radiopaque markers 27 and 24 are next to each other. Thisprovides a visual indication during fluoroscopy.

The proximal end of the injector tubes 15 are held by a manifold 17 thatis attached inside the distal end of the outer tube 16 and the core wire11. The proximal end of the outer tube 16 is attached to a hypotube 18that continues to the proximal end of the INAS 10. The hypotube 18 istypically made from a metal like 316 Stainless steel and the outer tube16 is made from a plastic or metal reinforced plastic so that it isflexible enough to allow the INAS to easily be advanced and retractedaround the bend in a typical guiding catheter such as that used forangioplasty or stenting of the renal arteries. The outer tube 16 wouldtypically be between 5 and 30 cm long although it is also envisionedthat the INAS 10 could be designed without a hypotube 18 and only aplastic or metal reinforced plastic outer tube 16 running to theproximal end.

The core wire 11 is attached to the inside of the hypotube 18 atjunction point 23. This attachment could for example be by adhesivemeans, welding or brazing. Spot welding is the preferred method. In thisway, the core wire 11 that supports the fixed wire 25 cannot be easilydetached form the INAS 10. The injector lumen 21 inside of the hypotube18 connects to the lumen of the outer tube 16 which is in fluidcommunication with the injector tube lumens 29 of each of the expandabletubes 15 allowing an ablative substance or solution to flow from theproximal end of the INAS 10 through the hypotube 18, through the outertube 16, through the expandable injector tubes 15 and out of thesharpened injector needles 19 into a vessel wall.

FIG. 2 is a schematic view of the distal portion of the INAS 10′ in itsclosed position as it would be configured for delivery into the humanbody or to cover the injection needles 19 during removal from the humanbody. The INAS 10′ includes fixed wire 25 with tip 28, core wire 11,outer tube 16 and sheath 12. In this configuration the two radiopaquemarkers 27 and 24 are adjacent to each other with the sheath 12 beingadvanced to it fully distal position. Of great importance in this designis that in the closed position, the sharpened needles 19 are completelyenclosed by the sheath 12 which is closed over the proximal portion ofthe tapered tip 26.

FIG. 3 is a schematic view of the distal portion of the presentinvention Intravascular Nerve Ablation System (INAS) 10 in its fullyopen position having a fixed guide wire 25 with tip 28 at its distalend. FIG. 3 shows the INAS 10 in its fully open position with theself-expanding injector tubes 15 with distal ends sharpened to forminjection needles 19 open to their maximum diameter. Flexible cords 13with adhesive 14 that attaches the cords 13 to the injector tubes 15 actas a penetration limiting member to prevent the distal tip of theneedles 19 from penetrating more than a maximum distance L shown inFIGS. 1 and 3 into a vessel wall.

A sheath 12 with radiopaque marker 27 is shown in FIG. 3 in its positionwhere it has been pulled back to allow full expansion of the injectortubes 15. There are 4 injector tubes 15 in this embodiment of the INAS.The distal section 20 of the INAS 10 includes the fixed distal wire 25,tapered flexible tip 26, radiopaque maker 24 and sheath engagementsection 22 that assures that the distal portion will properly pull backinto the sheath 12 following use of the INAS 10 to ablate tissue in avessel of the human body. Also shown in FIG. 3 are the outer tube 16with injection lumen 21 and core wire 11.

FIG. 4 is a longitudinal cross sectional drawing of the proximal end ofthe fixed wire embodiment of the INAS 10 of FIGS. 1 through 3. Thehypotube 18 with injection lumen 21 also shown in FIG. 1, has a Luerfitting 35 with lumen 36 attached to its proximal end allowing a sourceof an ablative substance of solution to be injected through the lumen 36of the Luer fitting 35 into the lumen 21 of the hypotube 18 andsubsequently out of the injection needles 19 of FIG2s. 1 through 3. Theproximal end of the sheath 12 is attached to the distal end of theTuohy-Borst fitting 30 with handle, 36, inner hub 33 washer 39 andO-Ring 43. As the handle 36 is tightened by screwing it down over theinner hub 33, the O-Ring will compress sealing the Tuohy-Borst fitting30 against the hypotube 18. A side tube 31 with Luer fitting 32 having alumen 34 is designed to allow the lumen 38 between the inside of thesheath 12 and hypotube 18 to be flushed with saline before insertion ofthe INAS 10 into a human body. Before insertion into the body, theTuohy-Borst fitting 30 is tightened onto the hypotube 18 with the sheath12 in its most distal position and the INAS 10′ closed as is shown inFIG. 2. When in the distal end of the INAS 10′ is properly positioned inone of the renal arteries, the Tuohy-Borst fitting is loosened and thehandle 36 is pulled in the proximal direction while the Luer fitting 35his held in place. This will open the INAS 10 and allow the injectortubes 15 of FIG. 1 to expand outward in the vessel.

FIG. 5A is a schematic view of the distal portion of the closed INAS 10′of FIG. 2 as it is first advanced out of a guiding catheter 80 into arenal artery just distal to the ostium with the aorta. The INAS 10′ isadvanced until the marker band 24 distal to the distal end of theguiding catheter 80. It is anticipated that an optimal distance of 5 to15 mm distal would work best although shorter and longer distances arepossible depending on the geometry of the renal artery and the distanceof penetration of the guiding catheter 80 into the ostium of the renalartery.

FIG. 5B is a schematic view of the distal portion of the closed INAS 10″as the sheath 12 is being pulled back to allow the expandable tubes 15open against the wall of the renal artery just distal to the ostium intothe aorta. In this position, it is desired that the angle A at which thedistal end of the injection needles engage the inside of the vessel wallshould be less than 80 degrees and ideally between 40 and 60 degrees. Ifthe angle is too large, the injection tubes could buckle backwardsinstead of pushing the sharpened needles into the vessel wall. If theangle is too small, the needles might not penetrate properly and mightslide distally along the inside of the vessel wall. After the sheath 12is pulled back so it no longer constrains the expandable injector tubes15, the INAS 10″ is then pushed in the distal direction allowing theinjector tubes 15 to continue their outward expansion as the injectionneedles 19 penetrate into the wall of the renal artery. The penetrationwill stop when the cords 13 engage the wall of the renal artery limitingthe penetration of the needles 19. Alternatively, this “cord” may bereplaced by a nitinol wire structure that is fixably attached to theinjector tubes 15 to provide a (stiffer) metallic penetration limitingmember.

FIG. 5C is a schematic view of the distal portion of the fully open INAS10 of FIG. 3 with needles 19 fully embedded into the wall of the renalartery to allow the infusion of an ablative substance into the vesselwall. Although FIG. 5C show the cords 13 fully expanded, it would betypical for them to be slightly less in diameter than their maximumdiameter when they engage the wall of the renal artery to limit thepenetration of the needles 19. Preferably, the maximum diameter of theINAS 10 system selected for the procedure should be at least 2 to 4 mmgreater than the inside diameter of the renal artery. For example, ifthe renal artery diameter at the desired ablation site is 5 mm indiameter, then a INAS 10 with maximum diameter of 7 to 9 mm should beselected. In the configuration of FIG. 5C, the ablative substance isinjected through the needles 19 into the wall of the renal artery. Thepreferred ablative substance is ethyl alcohol (ethanol), which hashistorically been used to ablate tissue, particularly nerve tissue inthe cardiovascular system. Other agents such as phenol, glycerol, localanesthetic agent(s) such as lidocaine, guenethidine or other cytotoxicand/or neurotoxic agents are also anticipated as possible injectates.

FIG. 5D is a schematic view of the distal portion of the closed INAS 10″as its distal portion is being pulled back into the sheath 12 to closethe INAS 10″ either for subsequent use in the other renal artery or forremoval from the body. A shaded area shows the ablated region 100 wherethe tissue in the wall of the renal artery has been ablated. If theneedle depth of penetration is set at a greater depth (e.g. 2.5-3 mm)the ablation zone may be deeper (primarily adventitial) and create lessinjury to the intimal and medial layers of the renal artery wall than isshown in 5D.

FIG. 5E is a schematic view of the distal portion of the closed INAS 10′of FIG. 2 after it has been closed by retraction of the distal portionof the INAS into the sheath 12 either for subsequent use in the otherrenal artery or for removal from the body.

For this embodiment of the INAS 10, the method of use for hypertensionwould be the following steps:

-   -   1. Remove the sterilized INAS 10 from its packaging in a sterile        field, flush the lumen 38 between the outer tube 12 and hypotube        18 with saline.    -   2. Advance the sheath 12 until the INAS 10′ is in its close        position.    -   3. Lock the Tuohy-Borst fitting 30 down onto the hypotube 18 of        FIG. 4.    -   4. Access the aorta via a femoral artery, typically with the        insertion of an introducer sheath.    -   5. Using a guiding catheter 80 of FIGS. 5A through 5E or a        guiding sheath with a shaped distal end, engage the first        targeted renal artery through the aorta. This can be confirmed        with contrast injections as needed.    -   6. Place the distal end of the INAS 10 in its closed position of        FIG. 2 into the proximal end of the guiding catheter 80. There        is typically a Tuohy-Borst fitting attached to the distal end of        a guiding catheter 80 to constrain blood loss.    -   7. The closed INAS 10 can be pushed through the opened        Tuohy-Borst fitting into the guiding catheter 80.    -   8. Advance the INAS 10 through the guiding catheter, until the        marker band 24 is distal to the distal end of the guiding        catheter within the renal artery as shown in FIG. 5A.    -   9. Pull the sheath 12 back in the proximal direction while        holding the Luer fitting 35 and hypotube 18 the proximal end of        the INAS 10 fixed. This will allow expansion of the injector        tubes 15 against the wall of the renal artery as shown in FIG.        5B.    -   10. Lock the Tuohy-Borst fitting 30 down on the hypotube 18.    -   11. With the Tuohy-Borst fitting at the proximal end of the        guiding catheter 80 loosened advance the sheath 12 and hypotube        18 locked together pushing the sharpened needles 19 into, or        through, the wall of the renal artery as the self-expanding        injector tubes 15 continue to expand outward. The injector tubes        15 will stop penetration when penetration limiting member 13        engages the wall of the renal artery thus limiting the        penetration of the needles 19 to the desired depth.    -   12. Attach a syringe or injection system to the Luer fitting 35        of FIG. 4 that provides ablative fluid that will be injected        into the wall of the renal artery    -   13. Inject an appropriate volume of ethanol (ethyl alcohol) or        other appropriate cytotoxic fluid, or combination of        neuroablative fluids, or heated fluid or steam (e.g., 90-95        degree heated saline solution) from the syringe or injection        system through the lumen 36 and out of the needles 19 into the        wall of the renal artery. A typical injection would be 1-10 ml.        This should produce a multiplicity of intersecting volumes of        ablation (one for each needle) that should create a torroid of        ablated tissue around the circumference of the renal artery as        shown as the ablated regions shown in FIGS. 5D and 5E. Contrast        and/or an anesthetic agent such as lidocaine can be injected        before or at the same time as the ablative fluid.    -   14. Loosen the Tuohy-Borst fitting 30 and while holding the        Tuohy-Borst fitting 30 and sheath 12 fixed, pull the Luer 35        with hypotube 18 in the proximal direction until the expandable        tubes 15 with needles 19 are fully retracted back into the        distal end of the sheath 12 and the marker bands 27 and 25 are        next to one another. This is shown in FIGS. 5D and 5E.    -   15. In some cases, one may advance the INAS 10 again into the        renal artery, rotate it between 20-90 degrees and then repeat        the injection to make an even more definitive volume of        ablation. This would be advantageous if the INAS 10 has fewer        than 4 injector tubes and should not be needed with the 4        injector tubes shown in herein.    -   16. The same methods as per steps 8-15 can be repeated to ablate        tissue around the other renal artery during the same procedure.    -   17. Remove the INAS 10 in its closed position from the guiding        catheter. Being in the closed position, the needles 19 are        enclosed and cannot harm the health care workers, or expose them        to blood borne pathogens.    -   18. Remove all remaining apparatus from the body.

A similar approach can be used with the INAS 10, to treat atrialfibrillation through a guiding catheter inserted through the septum intothe left atrium with the wall of the target vessel being the wall of oneof the pulmonary veins.

FIG. 6 is a longitudinal cross section drawing of the distal portion ofanother embodiment the present invention Vascular Nerve Ablation System(INAS) 40 that is delivered over a separate guide wire 60. FIG. 6 showsthe INAS 40 in its fully open position with the self-expanding injectortubes 45 with distal ends sharpened to form needles 49 open to theirmaximum diameter. Flexible cords 43 connect the injector tube 45 and actas a penetration limiting member to prevent the distal tip of theneedles 49 from penetrating more than a maximum distance D into a vesselwall. Unlike the cord 13 of FIG. 1, the cords 43 are fed though holes 57in the sides of each injector tube 45 a distance D from the distal end.A drop of adhesive (not shown) can be used to seal the holes and preventleakage of the ablative substance or solution during injection into avessel wall.

A sheath 42 is shown in its position where it has been pulled back toallow full expansion of the injector tubes 45. There are 4 injectortubes 45 in this embodiment of the INAS 40 although as few as 2 and asmany as 12 are envisioned. The distance D can be between 0.2 and 2 mmwith the optimal being about 0.5-1 mm.

The proximal end of the injector tubes 45 are held by a manifold 47 thatis attached inside the distal end of the outer tube 46 and the innertube 48. An injection lumen 51 lies between the inner tube 48 and outertube 46 proximal to the manifold 47. Ablative material injected throughthe injection lumen 51 will flow into the proximal ends of the injectortubes 45 and then out of the injection needles 49 into one or morelayers of the blood vessel and/or into the volume of tissue just outsidethe vessel wall.

The distal section 50 of the INAS 40 that is coaxially attached to thedistal section of the inner tube 48 includes the tapered flexible tip56, radiopaque maker 55 and sheath engagement section 54 that assuresthat the distal portion of the INAS 40 will properly pull back into thesheath 42 following use of the INAS 40 to ablate tissue in a vessel ofthe human body. The guide wire 60 can be advance and retracted in thelongitudinal direction inside of the guide wire lumen 41 that liesinside of the inner tube 48. The INAS 40 can be configured either as anover-the-wire or a rapid exchange device. If over-the-wire, the guidewire lumen 41 inside of the inner tube 48 runs all the way to theproximal end of the INAS 40 as is shown in FIG. 7. If a rapid exchangeconfiguration is used then the guide wire would exit from the INAS 40and run external to the outside of the INAS 40 for some portion of thelength of the INAS 40. If a rapid exchange is used then a slot will beneeded in the sheath 42 to allow for the sheath 42 to movelongitudinally with respect to the rest of the INAS 40. The proximal endof the rapid exchange configuration would be identical to that of thefixed wire INAS 10 of FIG. 4. The guide wire would typically run outsideof the body of the INAS 40 for at least the most proximal 10 cm with thepreferred embodiment having the guide wire exit through the side of theouter tube 46 and sheath 42 between 5 and 15 cm from the distal end ofthe INAS 40.

FIG. 7 is a longitudinal cross sectional drawing of the proximal end 70of an over-the-wire embodiment of the INAS 40 of FIG. 6. The inner tube48 has a Luer fitting 78 attached to its proximal end. The guide wire 60can be advanced through the guide wire lumen 41 inside of the inner tube48. The proximal end of the outer tube 46 is attached to the hub 79 thatis sealed against the inner tube 48, forming the injection lumen 51between the inner tube 48 and outer tube 46. A side tube 74 with lumen76 connects into the hub 79 with a Luer fitting 75 attached to theproximal end of the side tube 74. A syringe or other injection devicecan be attached to the Luer fitting 75 to inject an ablative substanceor solution through the lumen 76 into the injection lumen 51 into theinjector tube 45 of FIG. 6 and out of the ends of the injection needles49 into a vessel wall. The proximal end of the sheath 42 connects to thehub 77 that acts as a handle to slide the sheath 42 coaxially over theouter tube 46 to open and close the INAS 40 of FIG. 6. A side tube 72with lumen 73 connects into the hub 77. A Luer fitting 71 it attached tothe proximal end of the side tube 72 to allow the lumen 62 between thesheath 42 and the outer tube 46 to be flushed with saline solutionbefore introduction of the INAS 40 in to the human body. While the hub77 shown here is a plastic member, it is envisioned that a Tuohy-Borstfitting such as the Tuohy-Borst fitting 30 of FIG. 4 could be used hereand could be advantageous as it would allow one to lock the sheath 42 inposition onto the outer tube 46 during insertion and removal from thebody so that the distal end of the sheath 42 would remain in its mostdistal position protecting the injection needles 49 and protectinghealth care workers from exposure to needle stick injury.

FIG. 8 is a longitudinal cross section of a disposable injector 90 foruse in providing ablative fluid heated to a preset temperature forinjection through the INAS 10 of FIGS. 1-5C to ablate tissue in a humanbody. The injector 90 includes a syringe 104 with fluid storage volume99 and female Luer fitting 93 that would typically attach to a standardstopcock (not shown) the stopcock being connected to the male Luerfitting 35 at the proximal end of the INAS 10 of FIGS. 1-4. It is alsoenvisioned that a stopcock could be provided with either the injector 90or INAS 10 or integrated into either. The syringe 104 is surrounded bythe heating coil 94 which is contained within the case 95 filled withheat insulation 96. The power for the heating coil 94 comes from thebattery 98 with positive terminal 91 and negative terminal 92 housed inthe battery case 97. A moveable plunger 101 with handle 102 and distalsealing gasket 103 is used to inject the heated ablative fluid in thevolume 99 through the Luer fitting 93 into the INAS 10 injector lumen 21of FIG. 4 where it will then flow out through the injector needles 19 ofFIGS. 1 and 3 into the tissue as shown in FIG. 5C. The injector 90 mayinclude closed loop electronics with either a display of the temperatureor one or more LEDs that let the user know when the ablative fluid inthe syringe 104 is at the desired temperature. The injector 90 could bemanufactured for a single preset temperature or be adjustable to morethan one temperature. While FIG. 8 shows a manual injection plunger 101,it is also envisioned that a fluid pump or mechanical system to depressthe plunger could be integrated into the injector 90. The use of heatedfluid to abate tissue may be either effective by having a normallybenign substance like normal saline heated to the point where the heatcauses the tissue ablation or the heat may act to improve the ablativeability of a fluid such as alcohol that is normally ablative at room orbody temperature.

FIG. 9 is a longitudinal cross section drawing of the proximal sectionof an injection needle 110 with lumen 111 and distal end 119, showingattached longitudinal memory metal wire penetration limiting members 114and 116 with proximal portions 112 and 113 respectively. These proximalportions 112 and 113 are attached (glued, welded or brazed) to theoutside 115 of the needle so that when the needles 110 are released frominside of the sheath 12 of FIGS. 1-4 the distal portion of the wires 114and 116 will assume their memory state as shown in FIG. 9 forming amember that will limit penetration of the needle tip 119 toapproximately a preset distance L2. Since most arteries have a similarthickness, the distance L2 can be set to ensure the ablative fluidinjected through the needle lumen 111 will emerge in the appropriatevolume of tissue. Selection of the appropriate volume can be set bydifferent values of L2 such that the injection can be set to be in themedia of the artery, the adventitia of the artery or outside theadventitia of the artery. While FIG. 9 shows two wires 114 and 116, onewire would also function to limit penetration or 3 or more wires couldalso be used. Ideally the wire(s) would be attached to the outside ofthe needle 115 on the sides circumferentially of the needle and not onthe inside or outside where the wires 114 and 116 would increase thediameter of the closed INAS 10 of FIGS. 1-4 before the sheath 12 ispulled back to deploy the needles.

It is also envisioned that an injector designed to deliver asuper-cooled ablative fluid into the INAS of FIGS. 1-4 could also beappropriate for this application.

An important aspect of the present invention is the circumferentialdelivery of the ablative fluid with respect to the vessel wall. Suchdelivery from one or more injection egress points must attack the nervetissue circumferentially and at the correct depth to ensure efficacy,and ideally to minimize injury to the healthy and normal cellularstructures of the intimal and medial layers. The circumferentialdelivery can be handled as described above in three different ways.

-   -   1. Injection into the vessel wall at three or more points around        the circumference of the vessel,    -   2. Injection into the space outside of wall of the        vessel—although this can be accomplished by a single        needle/egress point, this is best done with at least two egress        points so that the needles can be kept small so as to allow the        vessel wall to reseal as the needles are retracted.    -   3. Injection into the inside to fill an annular space and        delivery the ablative fluid circumferentially to the inside        surface of the vessel.

FIG. 10 is a schematic view of yet another embodiment of the distalportion of the present invention Intravascular Nerve Ablation System(INAS) 200 in its fully open position having a fixed guide wire 225 withtip 228 at its distal end. FIG. 10 shows the INAS 200 in its fully openposition with the self-expanding injector tubes 215 with distal endssharpened to form injection needles 219 open to their maximum diameter.In this embodiment the injector tubes 215 each have a double bend orkink 214 having length L4 in the circumferential direction. The kinks214 act as a penetration limiting member to prevent the distal tip ofthe needles 219 from penetrating more than a maximum distance L3 into avessel wall.

A sheath 212 with radiopaque marker 227 is shown in FIG. 10 in itsposition where it has been pulled back to allow full expansion of theinjector tubes 215. There are 3 injector tubes 215 in this embodiment ofthe INAS. The distal section 220 of the INAS 200 includes the fixeddistal wire 225, tapered flexible tip 226, radiopaque maker 224 andsheath engagement section 222 that assures that the distal portion willproperly pull back into the sheath 212 following use of the INAS 200 toablate tissue in a vessel of the human body. Also shown in FIG. 10 arethe outer tube 216 with injection lumen 221 and core wire 211. The INAS200 of FIG. 10 would be used in the same way as the INAS 10 of FIGS. 1through 5E with the difference being the use of the kinks (double bends)214 as the penetration limiting members. The kinks 214 being integratedinto the injector tubes 215 as compared with the penetration limiter ofFIGS. 1-5E which are attached to the injector tubes. Adding the kinks214 should be a matter of setting a double bend into the shape of thememory metal (e.g. NITINOL) tubing used to form each of the injectortubes 215 that have sharpened ends that form the injection needles 219.In this embodiment the injector tubes themselves limit the penetrationinto the wall of a target vessel. Processes for shaping and heattreating NITINOL tubing to set the memory are well known.

The present invention has discussed use of the INAS for ablating tissuein the human body. It may also have merit for intravascular injection ofany fluid or medication. The ability to limit the depth of penetrationallows it to inject any fluid selectively into the media, adventitia oroutside of the adventitia of a blood vessel. It is also envisioned thatthe use of the double bend penetration limiting member concept of FIG.10 could be applied to any application where fluid injection is requiredat a preset distance into human tissue.

The term circumferential delivery is defined here as at least threepoints of simultaneous injection spaced circumferentially within avessel wall, or circumferential filling of the space outside of theadventitial layer (outer wall) of a blood vessel.

FIG. 11 is a longitudinal cross section of the another embodiment of thepresent invention INAS 300 in its closed position having four injectortubes 316 that can slide within four guide tubes 315 having expandabledistal portions. The injector tubes 316 with sharpened needles 319 haveinjection egress ports 317 near the distal end of each injector tube316. A sheath 312 with distal radiopaque marker band 327 encloses theguide tubes 315 with coaxial injector tubes 316. The injector tubes 316have injection lumens 321. The distal end of each of the guide tubes 329are tapered to provide a surface that will be approximately parallel tothe vessel wall when the guide tubes 315 expand outward duringdeployment. The distal portion of the guide tubes 315 having a length L5are set in an expanded memory shape and as shown in FIG. 11 areconstrained by the sheath 312 to prevent expansion. The four guide tubes315 are not attached or connected to the core wire 311 over the distanceL5. Proximal to the distance L5 the guide tubes 315 are attached orconnected to the core wire 311 with the preferred embodiment shown inFIG. 13 where the core wire 311 and four guide tubes 315 are embedded ina plastic cylinder 305.

The INAS 300 distal end has a tapered section 326 attached to a distalshapeable fixed guide wire 320 with wire wrap exterior 325, core wire311 and tip 328. The tapered section 326 includes a radiopaque marker324 and proximal taper 323 to facilitate closing the sheath 312 over theproximal section 323 following deployment of the INAS 300 to injectablative fluid into a vessel wall.

FIG. 12 is an enlargement of the area S12 of the INAS 300 of FIG. 11showing guide tubes 315 located coaxially inside of the sheath 312. Thedistal portion of the injector tubes 316 having sharpened needles 319,lumens 321 and injection egress ports 327 are located coaxially insideof the distal portion of the guide tubes 315 with tapered distal ends329. All or a portion of the needles 319 or the entire injector tube(s)may be made of a radiopaque material such as tantalum, platinum or gold.It is also envisioned that the ends of the needles may be coated orplated with a radiopaque material such as gold or that a platinum insertis placed into the distal tip of the injection tube prior to sharpeningthe tip into a cutting needle. Also shown are the core wire 311 and theproximal section 323 of the tapered section 326. It is also envisionedthat a distal portion including the distal end 329 of the guide tubes315 may also be made of, coated or plated with a radiopaque materialsuch as gold.

FIG. 13 is a circumferential cross section at S13-S13 of the INAS 300 ofFIG. 11 clearly showing the four guide tubes 315 attached to the outsideof the core wire 31. The injector tubes 316 with injection lumens 321are located coaxially inside of the guide tubes 315. The injection tubes316 are free to slide in the longitudinal direction within the lumens ofthe guide tubes 315. The injection tubes 316 could also be formed fromnitinol and pre-shaped to parallel the curved distal shape of the guidetubes 315 to enhance the coaxial movement of the injector tubes 316within the guide tubes 315. The guide tubes 315, injection tubes 316 andcore wire 311 lie coaxially within the sheath 312 which is free to slideover these parts. It is also shown how the guide tubes 315 and core wire311 are be embedded in plastic 305 to better hold the parts together orthey could be joined by welding, brazing of use of an adhesive. The useof the plastic 305 also allows a cylindrical surface to which theproximal portion of the sheath 312 can seal to allow flushing of thespace between the inside of the sheath 312 and the outside of theplastic 305 with saline before the start of device use.

FIG. 14 is a longitudinal cross section of the expanded distal portionof the INAS 300′ in the fully open configuration with the injectiontubes 316 shown advanced beyond the distal end of the guide tubes 315.The distal end of the injector tubes 316 has the sharpened needles 319with injection egress ports 317.

In this configuration the sheath 312 has been pulled back to allow theguide tubes 315 to expand outward. The guide tubes 315 are typicallymade from a memory metal such as NITINOL. The injector tube 316 may bemade from any metal such as 316 surgical grade stainless steel or mayalso be made from NITINOL or a radioopaque metal such as tantalum orplatinum. If the elements 315 and 316 are not fabricated from aradio-opaque metal it is envisioned that distal portion of the injectortube(s) 316 and guide tube(s) 315 would be coated with a radio-opaquematerial such as gold, typically at or near the distal end of thetube(s) or a piece of radiopaque material may be used to form or belocated near the sharpened needles 319 at the distal end of the injectortubes. The diameter L6 denotes the memory configuration for the fullyopen guide tubes 315. For use in the renal arteries, L6 would typicallybe between 3 and 10 mm with 8 mm being a best configuration if only onesize is made as very few renal arteries are larger than 7 mm diameter.Also shown in FIG. 14 are the distal ends 329 of the guide tubes 315that in the fully open configuration are parallel to the longitudinalaxis of the INAS 300′. The distal portion of the INAS 300′ has thetapered section 326 attached to the fixed guide wire 320 with tip 328,outer layer 325 and core wire 311.

FIG. 15 is an enlargement of the area S15 of FIG. 14 as it would appearwith the distal end of the injector tube 316 with lumen 321 and distalneedle 319 fully advanced beyond the distal end 329 of the guide tube315. Also shown in FIG. 15 is the arterial wall with internal elasticlamina (IEL), Media, External Elastic Lamina (EEL) and adventitia. FIG.14 shows that the injection egress ports 317 are placed into the heartof the adventitia.

An important feature of the present invention INAS 300 is that thepenetration depth for injection through the injection egress ports isadjustable so that any of the following can be accomplished.

-   -   1. Injection into the media    -   2. Injection into the media and adventitia by positioning one of        the injection egress holes in each.    -   3. Injection into the adventitia as shown in FIG. 15,    -   4. Injection into both the adventitia and the volume outside of        the adventitia and    -   5. Injection only into the volume outside the adventitia.

Specifically, the distance L7 that the tip of the needle 319 extendsbeyond the end 329 of the guide tube 315 can be adjusted using theapparatus in the proximal end of the INAS 300

FIG. 16 is a longitudinal cross section of the proximal end of the INAS300 of FIGS. 11-15. Three handles, the proximal injection handle 330,the central guide tube handle 340 and the distal sheath control handle350 allow the relative longitudinal movement of the sheath 312, guidetubes 315 and injector tubes 316. The position shown for FIG. 16 has thesheath control handle 350 in its most proximal position which wouldindicate the sheath 312 has been fully pulled back in the proximaldirection which would allow the guide tubes 315 to expand outward asshown in FIG. 14. The gap with distance L8 between the injection handle330 and the guide tube handle 340 can be adjusted using the screwadjustment piece 334 with screw threads 335 that allow it to move withrespect to the proximal portion 333 of the injection handle 330. The gapL8 as set will limit the penetration of the needles 319 and injectionegress ports 317 of the injector tubes 316 into the wall of the targetvessel. Ideally, a scale can be marked on the proximal portion 333 ofthe proximal injection handle 330 so that the medical practitioner canset the gap L8 and thus adjust the penetration distance. A luer fitting338 with access tube 336 is the port for ablative fluid injection intothe handle central lumen 332 which is in fluid communication with thelumens 321 of the injector tubes 316.

The central guide tube handle 340 includes an outer portion 342, asealing member 344 that seals the distal portion of the core wire 311 tothe outer portion 342 and provides four holes through which the fourinjector tubes 316 can slide into the proximal ends of the guide tubes315. A Luer fitting 348 with access tube 346 provides access to thespace between the injector tubes 316 and the guide tubes 315 throughholes in the guide tubes 347.

The distal sheath control handle 350 includes a distal portion 354attached to the outside of the sheath 312 with Luer fitting 358 and sidetube 356 providing access to the lumen under the sheath 312 to allow itto be flushed with saline before the procedure begins. The handle 350also has proximal portion 352 and elastic washer 359 that is compressedby screwing the proximal portion 352 into the distal portion 354 to lockthe position of the sheath 312 with respect to the guide tubes 315.

FIG. 17 is an enlargement of the area S17 of FIG. 16 showing theinjection handle 330 with proximal Luer fitting 338 attached to the sidetube 336 with lumen 331. The proximal portion 333 is sealed against theoutside of the side tube 336 and also seals against the outside of thefour injector tubes 316. This sealing can be by an adhesive or bymolding or forming the proximal piece onto the tubes 336 and 316. Thelumen 331 of the side tube 336 is in fluid communication with thecentral lumen 332 of the proximal portion 333 which is in fluidcommunication with the lumens 321 of the injector tubes 316. Thus anablative fluid injected through the Luer 338 will flow into the lumens321 of the injector tubes 316 and will emerge through the injectionegress ports 317 shown in FIG. 15 into the tissue in or near the wall ofthe target vessel. The screw threads 335 on both the proximal portion333 and screw adjustment piece 334 of the injection handle 330 allowadjustment of the gap L8 of FIG. 16. The gap L8 as set will limit thepenetration of the needles 319 and injection egress ports 317 of theinjector tubes 316 into the wall of the target vessel. Ideally, a scalecan be marked on the proximal portion 333 of the injection handle 330 sothat the medical practitioner can set the gap L8 and thus adjust thepenetration distance.

FIG. 18 is an enlargement of the area S18 of FIG. 16 showing the centralguide tube handle 340 and the sheath control handle 350.

The central guide tube handle 340 includes an outer portion 342, asealing member 344 that attaches the distal portion of the guide tubes315 and core wire 311 to the outer portion 342. The outer portion 342seals against the plastic 305 in which the guide tubes 315 and core wire311 are embedded. Proximal to the proximal end of the plastic 305, aLuer fitting 348 (shown in FIG. 15) with access tube 346 provides accessto the space between the injector tubes 316 and the guide tubes 315through holes 347 in the guide tubes 315.

The distal sheath control handle 350 includes a distal portion 354attached to the outside of the sheath 312 with Luer fitting 358 (shownin FIG. 15) and side tube 356 providing access to the lumen between thesheath 312 and the plastic 305 to allow it to be flushed with salinebefore the procedure begins. The handle 350 also has proximal portion352 and elastic washer 359 that is compressed by screwing the proximalportion 352 into the distal portion 354 to lock the position of thesheath 312 onto the plastic 305. In this locked position with the INAS300 closed as shown in FIG. 11 the INAS 300 is advanced into the bodyuntil the distal end with the marker band 324 of FIG. 11 is in the renalartery. The proximal portion 352 is then loosened so that the sheathcontrol handle 350 can be pulled in the distal direction while holdingthe central guide tube handle 340 fixed. It is envisioned that when theproximal end of the sheath control handle proximal piece 352 touches thedistal end of the outer portion 342 of the guide tube handle 340 asshown in FIG. 18, that the sheath 312 will be full retracted to allowexpansion of the guide tubes 315 against the wall of the target vessel.

The full procedure for renal denervation using the INAS 300 is asfollows:

-   -   1. Remove the sterilized INAS 300 from its packaging in a        sterile field, flush the injection lumens 321 of the injector        tubes and the space between the sheath 312 and plastic 305 and        injector tubes 316 and guide tubes 315 with saline.    -   2. Access the aorta via a femoral artery, typically with the        insertion of an introducer sheath.    -   3. Using a guiding catheter 80 of FIGS. 5A through 5E or a        guiding sheath with a shaped distal end, engage the first        targeted renal artery through the aorta. This can be confirmed        with contrast injections as needed.    -   4. Place the distal end of the INAS 300 in its closed position        of FIG. 11 into the proximal end of the guiding catheter. There        is typically a Tuohy-Borst fitting attached to the distal end of        a guiding catheter 80 to constrain blood loss.    -   5. The closed INAS 300 is then pushed through the opened        Tuohy-Borst fitting into the guiding catheter.    -   6. Advance the INAS 300 through the guiding catheter, until the        marker band 324 is distal to the distal end of the guiding        catheter within the renal artery.    -   7. Pull the sheath 312 back in the proximal direction while        holding the guide tube handle 340 fixed. This will allow        expansion of the injector tubes 315 against the wall of the        renal artery as shown in FIG. 15.    -   8. Lock the sheath control handle 350 down on the plastic 305.    -   9. Lock the Tuohy-Borst fitting at the proximal end of the        guiding catheter down onto the sheath 312    -   10. Advance the guide tube handle 340 to be sure the distal ends        329 of the guide tubes 315 are in good contact with the wall of        the renal artery and flaring outward in order to point more        closely to perpendicular to the long axis of the renal artery        wall.    -   11. While holding the guide tube handle 340 fixed, advance the        injection handle 330 until its distal end touches the proximal        end of the guide tube control handle 340. This will cause the        needles 319 to advance through the distal ends 329 of the guide        tubes 315 into the wall of the target vessel to the appropriate        penetration limited by the two handles 330 and 340 touching.    -   12. Attach a syringe or injection system to the Luer fitting 338        that provides ablative fluid that will be injected into the wall        of the renal artery. One could optionally inject an anesthetic        drug like lidocaine and/or contrast media before the ablative        fluid to prevent or reduce the pain associated with the        procedure and/or ensure the needles are in the right position.        It is also conceived that an anesthetic or contrast can be        combined with the ablative fluid.    -   13. Inject an appropriate volume of the ablative fluid from the        syringe or injection system through the lumens 321 of the        injector tubes and out of the injection egress ports 317 into        and/or outside of the wall of the renal artery. A typical        injection would be 1-10 ml. This should produce a multiplicity        of intersecting volumes of ablation (one for each needle) that        should create a torroid of ablated tissue around the        circumference of the renal artery as shown as the ablated        regions shown in FIGS. 5D and 5E.    -   14. While holding the guide tube handle 340 fixed. Pull the        injection handle 330 in the proximal direction retracting the        needles 319 back into the guide tubes 315.    -   15. Unlock the sheath control handle 350 from the plastic 305        and while holding the guide tube control handle 340 fixed,        advance the sheath control handle 350 in the distal direction        until the guide tubes 315 are fully collapsed back into the        distal end of the sheath 312 and the marker bands 327 and 324        are next to one another indicating that the INAS 300 is now in        its closed position as shown in FIG. 11.    -   16. The same methods as per steps 6-15 can be repeated to ablate        tissue around the other renal artery during the same procedure.    -   17. Remove the INAS 300 in its closed position from the guiding        catheter. Being in the closed position, the needles 319 are        doubly enclosed within the guide tubes 315 which are inside the        sheath 312 so the sharpened needles 319 cannot harm the health        care workers, or expose them to blood borne pathogens.    -   18. Remove all remaining apparatus from the body.

A similar approach can be used with the INAS 300, to treat atrialfibrillation through a guiding catheter inserted through the septum intothe left atrium with the wall of the target vessel being the wall of oneof the pulmonary veins.

FIG. 19 is a longitudinal cross section of the proximal portion of analternate embodiment of the INAS 400 which simplifies the design ascompared to the INAS 300 proximal portion of FIG. 16. The INAS 400 usesthe identical distal portion design as the INAS 300 of FIGS. 11-15.Three handles, the proximal injection handle 430, the central guide tubehandle 440 and the distal sheath control handle 450 allow the relativelongitudinal movement of the sheath 312, middle tube 415 and inner tube416 with injection lumen 421. The position shown for FIG. 19 has thesheath control handle 450 near its most proximal position which wouldindicate the sheath 312 has been pulled back in the proximal direction.In this position, as with the INAS 300 of FIGS. 11-18 this will causethe distal portion of the guide tubes 315 to expand outward as shown inFIG. 14.

The gap with distance L9 between the injection handle 430 and the guidetube handle 440 can be adjusted using the screw adjustment piece 434with screw threads 435 that allow it to move with respect to theproximal portion 433 of the proximal injection handle 430. The proximalend of the screw adjustment piece 434 is the penetration limiting memberthat will limit to the distance L9, the penetration of the needles 319and injection egress ports 317 of the injector tubes 316 into the wallof the target vessel. Ideally, a scale can be marked on the proximalportion 433 of the handle 430 so that the medical practitioner can setthe gap L9 and thus adjust the penetration distance. The central tube416 with lumen 421 is sealed into the proximal piece 433 of the proximalinjection handle 430. A luer fitting 438 with access tube 436 is theport for ablative fluid injection into the handle lumen 432. The lumen439 of the Luer fitting 438 is in fluid communication with the lumen 437of the access tube 436 which is in fluid communication with theinjection lumen 421 of the inner tube 416. The inner tube 416 istypically a metal hypertube although a plastic tube or plastic tube withbraided or helical wire reinforcement is also conceived.

The central guide tube handle 440 attached to and controlling thelongitudinal movement of the middle tube 415 includes a proximal portion444 that can screw into a distal portion 442. When screwed in to thedistal portion 442, the proximal portion 444 will compress the washer445 allowing the handle 440 to be locked down onto the middle tube 415.This is also needed during preparation for use when the Luer fitting 448with side tube 446 can be used to flush the space between the inner tube416 and middle tube 415 with saline solution.

The distal sheath control handle 450 attached to and controlling thelongitudinal movement of the sheath 312 includes a proximal portion 454that can screw into a distal portion 452. When screwed in to the distalportion 452, the proximal portion 454 will compress the washer 455allowing the handle 450 to be locked down onto the sheath 312. This isalso needed during preparation for use when the Luer fitting 458 withside tube 456 can be used to flush the space between the middle tube 415and sheath 312 with saline solution.

FIG. 20 is a longitudinal cross section of a central transition portion460 connecting the proximal portion of the INAS 400 of HG. 19 with thedistal portion of the INAS 300 of FIGS. 11-15. The proximal end of thecentral transition portion 460 includes the same three concentric tubeslocated at the distal end of the handle portion of the INAS 400 shown inFIG. 19. Specifically, the proximal end of the transition portion 460includes the inner tube 416 with injection lumen 421, the middle tube415 and the sheath 312. At the distal end of the inner tube 416, amanifold 410 is inserted which seals the inner tube 416 to the fourinjector tubes 316 such that the lumen 421 of the inner tube 416 is influid communication with the lumens 321 of the four injector tubes 316.In addition, longitudinal motion of the inner tube 416 will therefore betranslated to longitudinal motion of the four injector tubes 316.

The middle tube 415 seals inside of the plastic member 405 which alsoseals to the guide tubes 315 and core wire 311. Longitudinal motion ofthe middle tube 415 will translate into longitudinal motion of the fourguide tubes 315. The sheath 312 is the same sheath as in the distalportions of the INAS 300 of FIGS. 11-15.

FIG. 21 is a circumferential cross section at S21-S21 of the centraltransition section 460 of FIG. 20. Looking in the distal direction, onesees in cross section, the three concentric tubes the sheath 312, middletube 415 and inner tube 416. Inside the inner tube one sees the proximalend of the manifold 410 and the proximal ends of the four injector tubes316. It can clearly be seen that the manifold 410 seals the fourinjector tubes 316 into the inner tube 416 and the lumens 321 of theinjector tubes 316 open into the lumen 421 of the inner tube 416.

FIG. 22 is a circumferential cross section at S22-S22 of the centraltransition section 460 of FIG. 20. Looking in the distal direction onesees in cross section, the sheath 312 and middle tube 415. The middletube 415 is sealed into the distal portion of the plastic member 405.One also sees the proximal end of the four guide tubes 315 and core wire411. It also shows how the four injector tubes 316 enter the proximalends of the guide tubes 315.

FIG. 23 is a circumferential cross section at S23-S23 of the centraltransition section 460 of FIG. 20. This cross section is identical tothe circumferential cross section shown in FIG. 13 showing the sheath312 and plastic member 405 (was 305 in FIG. 13) that seals and attachestogether the four guide tubes 315 and the core wire 311. The injectortubes 316 lie concentrically inside of the four guide tubes 315. Thus,FIGS. 20-23 clearly show how the simplified proximal end of FIG. 19connects to the distal portion of the INAS 300 of FIGS. 11-15.

While this description has focused on use of the INAS for use inablation of tissue, it is also clearly envisioned that the apparatus andmethods of FIGS. 1-23 can be applied to the use of this apparatus toinject any fluid for any purpose including that of local drug deliveryinto a specified portion of a blood vessel or the volume of tissue justoutside of a blood vessel.

Various other modifications, adaptations, and alternative designs are ofcourse possible in light of the above teachings. Therefore, it should beunderstood at this time that within the scope of the appended claims theinvention may be practiced otherwise than as specifically describedherein.

1. A intravascular nerve ablation system for circumferential delivery ofan ablative fluid in or outside the vessel wall of a target vesselcomprising: a catheter body having a central axis extending in alongitudinal direction having a fluid injection lumen, the fluidinjection lumen being in fluid communication with three or moresharpened injection needles, the catheter body further including adistal tip and an outer sheath, the outer sheath having a first closedposition where the sheath and the distal tip together enclose thesharpened injection needles, the sheath having a second open position,the open position allowing the injection needles to expand outward intothe inside vessel wall of a target vessel; an external source ofablative fluid in fluid communication with said fluid injection lumen,and injection egress located near the distal end of the needles adaptedto provide circumferential delivery of the ablative fluid from the fluidinjection lumen at a prescribed depth of injection.
 2. The system ofclaim 1 where the circumferential delivery of the ablative fluid is intoa specific volume of tissue selected from: the media of the wall of thetarget vessel, the adventitia of the wall of the target vessel, thevolume outside of the adventitia of the wall of the target vessel, Themedia and adventitia of the wall of the target vessel, The adventitiaand the volume outside of the adventitia of the target vessel.
 3. Thesystem of claim 1 where the circumferential delivery includes at leastthree points of injection egress.
 4. The system of claim 1 furtherincluding a distal balloon to prevent the ablative fluid from flowingdownstream in the target vessel.
 5. The system of claim 1 where saidcatheter body includes a fixed guide wire attached to its distal end. 6.The system of claim 1 configured to be advanced coaxially over aseparate guide wire.
 7. The system of claim 1 where the injection egressis provided by at least one injector tube having an injection needle atits distal end, the injection egress being near the distal end of theinjection needle.
 8. The system of claim 1 further including a distalself-expanding portion.
 9. The system of claim 8 where the distalself-expanding portion includes the injection egress.
 10. The system ofclaim 8 where the distal self-expanding portion includes at least oneguide tube, and the injection egress is provided by at least oneinjector tube having a needle at its distal end, the at least oneinjector tube adapted to be advanced and retracted through the at leastone guide tube.
 11. The system of claim 8 further including a sheaththat when retracted to its most proximal open position allows the distalself-expanding portion to expand outward.
 12. The system of claim 11where said sheath has a distal closed position and a proximal openposition, where the sheath in the closed position extends in the distaldirection so as to completely cover the injection egress.
 13. The systemof claim 11 further including a sheath that includes a radiopaque markerat its distal end.
 14. The system of claim 8 where the self-expandingportion is formed from NITINOL.
 15. The system as of claim 1 where saidablative fluid includes at least one of the ablative fluids selectedfrom the group including ethanol, phenol, glycerol, lidocaine,bupivacaine, tetracaine, benzocaine, guenethadine, botulinum toxin. 16.The system of claim 1 where said ablative fluid is a heated fluidcomposition.
 17. The vascular nerve ablation system of claim 1 wheresaid ablative fluid is a cooled fluid composition.
 18. The vascularnerve ablation system of claim 1 where said ablative fluid is a form ofsteam injected through the injection lumen of the catheter body.
 19. Amethod of treating hypertension, the method including the steps of: a.placing an introducer sheath into the femoral artery; b. placing aguiding catheter through the introducer sheath; c. engaging the ostiumof a renal artery with the distal end of the guiding catheter; d.advancing a intravascular nerve ablation system in its closed positionthrough the guiding catheter until the distal end of the intravascularnerve ablation system lies within a renal artery distal to the distalend of the guiding catheter, the vascular nerve ablation systemincluding a distal portion with injection egress adapted to providecircumferential delivery of an ablative fluid to ablate the sympatheticnerves in proximity to the renal artery e. positioning the injectionegress for circumferential delivery of the ablative fluid f. deliveringablative fluid through the injection egress at a prescribed depth; g.retracting the vascular nerve ablation system into the guiding catheter;h. repeating steps a through h for the other renal artery as needed;and, i. removing the vascular nerve ablation system from the body of thepatient.
 20. The method of claim 21 where the injection egress providescircumferential delivery of the ablative fluid targeted to the depth ofthe media of the renal artery.
 21. The method of claim 21 where theinjection egress provides circumferential delivery of the ablative fluidtargeted to the depth of the adventitia of the renal artery.
 22. Themethod of claim 21 where the injection egress provides circumferentialdelivery of the ablative fluid targeted to a depth outside of theadventitia of the renal artery.
 23. An intravascular nerve ablationsystem for circumferential delivery of an ablative fluid to a volume oftissue in proximity to the vessel wall of a target vessel comprising: acatheter body having a central axis extending in a longitudinaldirection and a fluid injection lumen; an external source of ablativefluid in fluid communication with said fluid injection lumen, and aguide tube having a distal end and a central lumen, the guide tubehaving a distal self-expanding portion. an injector tube having aninjection lumen in fluid communication with the fluid injection lumen ofthe catheter body. The injector tube located coaxially inside of theguide tube, the injector tube having a sharpened injection needle withinjection egress at its distal end, the injector tube being adapted toslide in the longitudinal direction within the guide tube. a guide tubehandle adapted to control the longitudinal motion of the guide tube. aninjection tube handle located near the proximal end of the catheter bodyincluding a port for injection of the ablative fluid, the port being influid communication with the fluid injection lumen of the catheter body,the injection handle further adapted to control the longitudinalmovement of the injector tube, the injection handle and guide tubehandle providing the means to limit the penetration into the vessel wallof a target vessel of the injection egress at the distal end of theinjector tubes.
 24. The system of claim 23 further including a sheathhaving a sheath located coaxially outside of the catheter body, thesheath having a closed position and an open position, the open positionallowing the self-expanding guide tube to expand outward against theinside of the wall of the target vessel.